2-substituted derivatives of 7-alkoxy-1,2,3,4 tetrahydro-8h-pyrido[1.2.]pyrazin - 8 - ones and 7 - alkoxy - 1,2,3,4,5,9-hexahydropyrido [1.2] [1.4] diazepin-9-ones and their derivatives



United States Patent 2,999 860 z-sunsnru'rnn nnnrvimvns on 7-ALKOXY- 1,2,3,4 TETRAHYDRO-8H-PYRIDO[1.2.]PYR- AZIN 8 ONES AND 7 ALKOXY 1,2,3,4,5,9- HEXAHYDROPYRIDO [1.2] [1.4] DIAZEPlN-9- ONES AND THEIR DERIVATIVES Carl Peter Krimmel, Mundelein, 111., assignor to G. D. Searle & (39., Chicago, 111., a corporation of Delaware No Drawing. Filed July 6, 1959, Ser. No. 824,929 11 Claims. (Cl. 260-268) The present invention relates to a new group of heterocyclic compounds and, more particularly, to the 2-substituted derivatives of 7-alkoxy-l,2,3,4-tetrahydro-8H-pyrido[l.2]pyrazin-8-ones and 7-alkoxy-l,2,3,4,5,9-hexahydropyrido[1.2] [l.4]diazepin-9-ones and their preparation. These compounds can be represented as the bases of the general structural formula wherein R is either a lower alkyl or a lower hydroxyalkyl radical and n is either 1 or 2.

In the foregoing structural formula the lower alkyl groups can be methyl, ethyl, straight-chain or branched propyl, butyl, amyl, or hexyl. In addition, the radical R can represent a lower alkyl radical of the same type with a hydroxy substituent.

The organic bases of this invention form pharmacem tically acceptable non-toxic salts with a variety of inorganic and strong organic acids including sulfuric, phosphoric, hydrochloric, hydrobromic, hydroiodic, suliamic, citric, lactic, maleic, malic, succinic, tartaric, cinnamic, acetic, benzoic, gluconic, ascorbic, and related acids. They also form quaternary ammonium salts with a variety of organic esters of sulfuric, hydrohalic and aromatic sulfonic acids. Among such esters are methyl chloride and bromide, ethyl chloride, propyl chloride, butyl chloride, isobutyl chloride, benzyl chloride and bromide, phenethyl bromide, naphthylmethyl chloride, dimethylsulfate, diethylsulfate, methyl benzenesulfonate, ethyl toluenesulfonate, ethylene chlorohydrin, propylene chlorohydrin, allyl bromide, methyallyl bromide and crotyl bromide.

The compounds of this invention can be prepared eonveniently using kojic acid as a starting material. Kojic acid is first converted to a l-hydroxymethyl--alkoxy-4- pyrone which is then reacted with a hydroxyalkylamine of the formula hydroxymethyl-S-alkoxy-4-pyridone of the structural formula p (lower alkyD-O CHgOH (Elia-(CH1) r-QH Heating of these compounds with thionyl chloride converts both hydroxy groups to chloro groups. The resulting 1 (w-chloroalkyl) 2 chloromethyl-5-alkoxy-4-pyridones have fungicidal activities against organisms of the type of Trichophyton mentagrophytes. They are also valuable intermediates for the preparation of the pyridopyrazines and pyridoazepines illustrated above. Thus, reaction with a monoalkyl amine or a hydroxyalkylamine yields the 2-alkyl or 2-hydroxyalkyl derivatives of the first formula shown herein. Reaction with a dialkylamine of the formula R NH, on the other hand, leads to the formation of the quarternary salt of the formula 0% or o N -n lj (lower alkyl)--- N\ /(C 2):

Further treatment of these pyridopyrazinium and pyridodiazepinium salts with a strong acid such as hydrochloric acid leads to the formation of an acid addition salt.

Two alternative processes are available for the preparation of these dicyclic compounds. Thus heating of a 2-hydroxymethyl-5-alkoxy-4-pyrone with a 2-dialkylaminoalkylamine yields a l-(2-dialkylannnoethyl)-2-hydroxymethyl-5-alkoxy-4-pyridone which, on contacting with thionyl chloride, is converted to the corresponding dihydrochloride of a l-(2-dialkylaminoethyl)-2-chloromethyl-S-alkoxy-4-pyridone. This can be made to undergo ring closure by heating with an amine such as aminopentane to yield the corresponding 2,2-dialkyl-7-alkoxy- 8 oxo 1,2,3,4 tetrahydro 8H pyrido[1.2]pyraziniurn chloride corresponding to the preceding general formula.

Heating of a 1 (2 dialkylaminoethyl) 2 hydroxyethyl-5-alkoxy-4-pyridone with thionyl chloride can also be made to yield, directly, the hydrochloride of a 2,2-dialkyl-7-alkoXy-8-oxo-1,2,3,4-tetrahydro 8H pyrido[1.2] pyrazinium chloride. The hydrogen chloride can be removed from this product by heating with an amine such as aminopentane.

The Z-substituted derivatives of 7-alkoxy-1,2,3,4-tetrahydro-8H-pyrido[1.2]pyrazine-8-ones and 7-alkoxy-1,2,3, 4,5,9-hexahydropyrido[1.2] [1.4] diazepin-9-ones of this invention have valuable pharmacological properties. They are fungicideseftective against organisms of the type of Trichophyton mentagrophytes. They also inhibit the action of hyaluronidase and have some ganglion blocking activity.

The compounds of the first formula given hereinabove wherein R represents a hydroxyalkyl group can be esterified with the acid halides of alkanoic acids and especially of alkanoic acids with aromatic substituents such as the phenylalkanoic acids and the polyphenylalkanoic acids to prepare pharmacologically valuable esters, e.g. central nervous depressants.

The invention will appear in further detail from the following examples which are given for the purposes of illustration only and are not to be construed as limiting the invention in spirit or in scope.

' Example 1 To a solution of 10 ml. of thionyl chloride and 20 ml. of chloroform is added with stirring 2.0 g. of l-g2-hydroxyethyl) 2 hydroxymethyl 5 methoxy-4-pyrrdone.

V oily phase becomes crystalline.

reaction .mixture is refluxed .on .the .steam .bath for 3.0 .minutes. During this interval, an oily phase separates from the reaction mixture. As refluxing is continued, the The crystals are filtered, washed with petroleum ether, and air-dried. After recrystallization by dissolving in refluxing absolute ethanol and diluting with anhydrous benzene, the hydrochloride of 1 (2-chloroethyl)-2-chloromethyl-5-meth0xy-4 pyridone is obtained. It is a White, water-soluble compound melting between l90-196 C. f

V The hydrogen chloride can be removed from the above compound by treatment with concentrated ammonium hydroxide. Thus, 5.0 g. of the hydrochloride is added to 40 of concentrated ammonium hydroxide at room temperature. 'by theseparation of white crystals from the reaction mixlure. After suction filtration and air drying, the product is recrystallized from butanone to give 1-(2-chloroethyl)- '2-.chloromethyl-S-methoxy-4 pyridone melting at about "151-152" C. By substituting 2.1 g. of 1-(2-hydroxyethyl)-2-hydroxymethyl-'5-ethoxy-4-pyridone as starting material, 1-(2- chloroethyl)-2-chloromethyl S-ethoxy-4-pyridone and its hydrochloride can be obtained.

Example 2 A mixture of -14 g. of 1-(3-hydroxypropyl')-2-hydroxymethyl-5-methoxy-4-pyridone, 40 ml. of thionyl chloride, and 150 ml. of chloroform is refluxed on the steam bath "for 1 5 minutes. The reaction mixtureisiconcentratedto Dissolution takes place at once followed 7 After evolution of hydrogen chloride has subsided, the

.ride dissolved in,10.0 ml. of methanol is added an equiva- A solution off8.2 g. of l-(Z-chloroethYl) 2-chloromethyl-5fmethoxy-4;pyridone hydrochloride in ml. ;of absolute ethanol and asolution of 112.1"g. of di-n-propylamine in 30ml. of absolute ethanol are mixed and refluxed on the steam bath for one hour. The reaction miXtllI'C'iS diluted with'300 m1. of butanone and seeded witha homologsuch as 2,2 diethyl 7 m'ethoxy-8-oxo-1,2,3,4-tetrahydro-8H- pyrido[l.2] pyrazinium chloride. The resultant crystallineprecipitateis filtered and dried in the steam. cabinet. It is recrystallized from hot anhydrous ,isopropanokand .driedat 100 C. for 5 hours in a vacuum to :give watersoluble, crystalline '2,2 dipropy1-7-methoxy8:oxo1,23,4-

halt-volume by evaporation in an 'openvessel and'the'n cooled. Scratching of the oily phase'yields crystals.

"These are filtered, Washed with petroleum ether, and :air-

"dried; Afterrecrystallization from anhydrous isoprotween 169-177" C. V The hydrogen chloride can be removed from the above compound by treatment with concentrated ammonium hydroxide as in the preceding example. After recrystallization from Z-butanone, the 'basemelts at "about '117-120 C. p

"Example 3 V .-A:solution of 300 mg. .of :1-(2-chloroethyl)-2-chloroimethyl-5 methoxy l-pyridone hydrochloride in 3 ml. of -absolute ethanol is mixed with a solution of 320mg. of :diethylamine in 3 ml. of absolute ethanol. ,The reaction -mixture is refluxed on the steam'bathtor one hour and ,cooledto room temperature. Anhydrous ethyl ether is then added with stirring until the first signs of perma- .nent turbidity appear. Scratching and standing cause a white precipitate to appear. .Seedcrystals will facilitate :this somewhat difiicult induction of precipitation. The precipitate is suction filtered and dried in the steamcabinet. ;It is recrystallized by dissolution in absolute ethanol at room temperature, seeding, and ether dilution. The product consists of white, water-soluble crystals melting 'at about 258-261? C. with decomposition to a red frothy :liquid; The '2,2-diethyl-7-methoxy-8-oxo-l,2,3,4-tetrahydro-SH-pyrido [1.21pyrazinium. chloride thus produced has :the structural formula V C231! zEs i To a stirred solution of 1.0 g. of 2:52 :diethyl:7-methoxytetrahydro-8H -pyrido [1.2] py'razinium chloridermeltiugzat about 229-232 C. with decomposition toa, frothy orange liquid.

4, Example 6 A mixture 'of 46.2 g. of l-(2-chloroethyl)-2-chloromethyl-5-methoxy-4-pyridone hydrochloride and an icecold solution of 30.0 g. of ethylamine in ml. of absolute ethanol is sealed in an ice-cold glass-lined bomb. The bomb is rocked and maintained at 86-102.,C. tor,one hour under a nitrogen pressure of,200-. 26O psi. The

bomb is then cooled to room temperature.

.To the stirred reaction mixture, :an excess of ,anhydrous hydrogen chloride-isopropanol solution is ;added,

specifically, 80.1111.v of a solution containing 0.265 .g. of

carbonate and. extracting with chloroform.

mple .A mixture of 4.1 goi-1-(2-chloroethyl)-2-chloromethyl-5-methoxy-4-pyridone hydrochloride,;5.2 g. of l-ami- .nopentane and 20 mL-of absolute ethanol is'stirred and refluxed on the steam bath for'one hour. Thereact-ion mixture is cooled andv made acid with a solution-of hydrogen chloride in anhydrous isopropanol :containing 0.25 g. of hydrogen chloride per ml. After the-reaction mixture sets to a thick slurry, 50ml. of anhydrous isopropanol is added to. aid in filtration. ,The slurry is suction filtered using a rubber dam. The filter cake is transterred to a drying cabinet with as littleexposure' to moist air 'as possible. The dry product is dissolved in the smallest'quantity of hot methanol inwhich it'will 'dissolve. This hot solution is then diluted with-twice its volume of anhydrous isopropanol. The solution is concentrated to half-volume on the steam bath. Cooling gives a white, crystalline slurry which .is suction filtered using a rubber dam. The filter cake is washed by suspensionin ethylacetate, suction filtered using a rubber dam, and dried in a-steam cabinet. .The product 'a'hoaseo is recovered as white, water-soluble microcrystals melting at 206-212 C. with decomposition to a frothy orange material. The 2-pentyl-7-methoxy-1,2,3,4-tetrahydro-8H- pyrido[l.2]pyrazin-8-one thus obtained has the structural formula Example 8 A solution of 4.4 g. of Z-aminoethanol in 20 ml. of absolute ethanol is added to 5.0 g. of 1-(2-chloroethyl)-2- chloromethyl-5-methoxy-4-pyridone hydrochloride. The reaction is exothermic and suitable allowances are therefore made in larger runs during the addition and subsequent heating. The reaction mixture is stirred and re- 611 on the steam bath for one hour and cooled. To the stirred reaction mixture is added 7 ml. of anhydrous hydrogen chloride-isopropanol solution having a concen- Iration of 0.265 g. of hydrogen chloride per milliliter. This treatment is followed by the addition of 200 ml. of anhydrous isopropanol. A gum is precipitated. This is crystallized by scratching and warming on the steam bath or more conveniently by the addition of homologous seed crystals.

p The crystallized gum is dissolved in ml. of hot methanol, treated with decolorizing carbon and filtered, The filtrate is diluted with ml. of anhydrous isopropanol, seeded, and warmed gently. The resultant crystals are filtered, washed on the filter with isopropmol, and dried in the steam cabinet. The product consists of white, wa- Ier-soluble crystals melting at about 194l96 C. to a clear frothy liquid. It is the dihydrochloride of 2,- (2 hydroxyethyl) 7 methoxy 8H pyrido[1.2]pyrazin-8-one of the structural formula Example 9 A solution of 5.4 g. of 3-amino-l-propanol in 20 ml. of absolute ethanol is added to 5.0 g. of l-(2-chloroethyl)- 2-chloromethyl-5-methoxy-4-pyridone hydrochloride. The reaction is exothermic and suitable allowances are therefore made in larger runs during the addition and subsequent heating. The reaction mixture is stirred and relluxed on the steam bath for one hour and cooled. To the stirred reaction mixture is added 7 ml. of hydrogen chloride-isopropanol solution having a concentration of 0.265 g. of hydrogen chloride per milliliter. If seed crystals are available, the introduction of the seeds at this point and dilution with fresh isopropanol and gradual warming on the steam bath Will lead directly to a crystalline precipitate. Lacking the seeds, a gelatinous white precipitate is formed. This gel is vigorously stirred and then allowed to stand in a covered vessel for one hour. It is suction filtered using a rubber dam. It is washed with isopropanol and dried in the steam cabinet. It is recrystallized by dissolving in a minimum of hot methanol, treating with decolorizing carbon, and filtering. The filtrate is diluted with an equal volume of anhydrous isopropanol, seeded, and filtered. After drying in the steam cabinet, the filter cake consists of white, water-soluble, non-hygroscopic crystals melting at about 205-209" C. with gassing to form a frothy white liquid.

An aqueous solution of 5.0 g'. of Z-(B-hydroxypropyD- 7 methoxy l,2,3,4 tetrahydro 8H pyrido[l.2]- pyrazin-8-one dihydrochloride thus obtained is saturated with potassium carbonate. The mixture is extracted with three 50 ml. portions of chloroform. The chloro- .form extracts are combined and dried over potassium carbonate. the steam bath to a clear, colorless viscous, syrup. The

The dn'edchloroforrn solution is evaporated on 6 a. syrup is crystallized by scratching. It islrecrystalliged by dissolving in 10 ml. of refluxing isopropanol, adding 30 ml. of butanone to the hot isop ropanol'solution and cooling. The solid product is filtered and dried in steam cabinet. It consists of white, water-soluble crystale of 2-(3-hydroxypropyl)-7-methoxy-1,2,3,4-tetrahy-* dro-8H-pyrido[1.21pyrazin-8-one melting at about 158-- 160 C. to. a colorless liquid.

Example 10 By the procedure of the preceding example, 10.9 g. of 1 (2-chloroethyl)-2-chloromethyl-S-methoxY-Lpyridone hydrochloride and 14.2 g. of 4-amino-2-butanql are reacted in 30 ml. of absolute ethanol. Following the reaction, the product is recovered as a white gelatinous precipitate by adding a hydrogen chlorideisopropanol solution containing 3.9 g. of hydrogen chloride in 415 ml. of anhydrous isopropanol. The precipitate is suction filtered using a rubber dam. It is washed on the filter with isopropanol, washed by suspension in butanone, and dried in the steam cabinet. Dissolution in hot anhydrous isopropanol and cooling again yields a white gel. After suction filtering with a rubber dam, drying in the steam cabinet, and comminuting, the 2 (3- hydroxbutyl) 7' methoxy l,2, 3, 4-tetrahydro-8H-pyrido-[1.2]pyrazin-8-one dihydrochloride is obtainedasaa white, water-soluble, powder melting at, -179 C. with gassing to a white frothy liquid.

Example 11 7 By the procedure of the preceding example, 6.0 g. of l-(S-chloropropyl)-2-chlorornethyl-5-methoxy-4-pyridone hydrochloride and 6.3 g. of 3-amino-l-propanol are caused to react in 25 ml. of absolute, ethanol. Following the reaction, the product is recovered; as a crystalline precipitate by adding a hydrogen chloride-isi ropanol solution containing 2.7 g. of hydrogen chloride in 310 ml. of anhydrous isopropanol, The isopropanol solution is then concentrated to a volume of approximately 200 ml, cooled, scratched, and seeded with a homolog. v

The crystalline product is filtered, washed on the. filter with isopropanol, and dried in the steam cabinet. It consists of White, water-soluble crystals melting at 198 201 C. with gassing to a White frothy liquid. The dihydrochloride of 2-(3-hydroxypropyl)-8-methoxy-1,2,3, 4,5 ,9-hexahydropyrido [1.21 [1.4] diazepin-9-one thus. .obtained has the structural formula (2H Cl Substitution of 5.0 g. of 1-aminopropane for the aminopropanol used in the foregoing procedure yields the dihydrochloride of 2-propyl-8-methoxy-1,2,3,4,5;9- hexahydropyridofll][l.4]diazepin-9-one of the structural formula Example 12 2,3,4-tetrahyd'ro-8H-pyrido[1.2]pyrazin-8-one thus obtained has the structural formulav Example 13 A mixture of 31.2 g. of Z-hydroxymethyl-S-rnethoxy- 4-pyrone, 23.2 g. of Z-diethylaminoethylamine and 40 ml. of water is stirred and refluxed on the steam bath for minutes. The reaction mixture is stripped of water by vacuum distillation on the steam bath.

Several drops of the residue are dissolved in isopropanol, diluted with anhydrous ethyl ether and/or benzene and dried over calcium sulfate. Seed crystals are obtained by scratching and cooling in an ice-bath.

The main body of the residue is dissolved in 600 ml. 'of hot ethyl acetate, treated with decolorizing carbon, filtered, cooled, and seeded. The resultant solid is recrystallized from hot ethyl acetate to give water-soluble crystalline 1 (Z-diethylaminoethyl) 2-hydroxymethyl-5- methoxy-4-pyridone melting at about 90-93? C.

v To a stirred solution of 50.0 g. of 1-(2-diethylaminoethyl)-2-hydroxymethyl-5-methoxy-4-pyridone in 200 ml. of chloroform, 75 g. of thionyl chloride is added. Addition is at such a rate as to initiate gentle reflux. Refluxing is contained for 10 minutes on the steam bath. During this operation, both "an orange oily phase and a solid phase separate from the reaction mixture. The reaction mixture is cooled causing substantial solidification of theoil phase.

Thehsolids are removed by suction filtration and the filter cake is washed by suspension in anhydrous ethyl ether. During each of these filtrations, the filter cake is exposed to atmospheric moisture as little as possible since it is hygroscopic under the conditions of the filtrations. The filter cake is dissolved in 200 ml. of Warm methanol, treated with decolorizing carbon, filtered and cooled. The methanol solution is seeded with the solid previously obtained. Itis then slowly diluted with 1800 ml. of acetone with stirring and gentle warming. Disregard forthese conditions may cause setting to a stiff voluminous gel. Employment of these conditions should result In a crystalline solid which may be accompanied by partial gel formation. In this case, continued Warming and scratching will convert the gel particles to a crystalline product which is suction filtered and dried in the steam cabinet. The 2,2-diethyl-7-n'1ethoxy-8-oxo-1,23,4- tetrahydro-SH-pyrido[1.21pyrazinium chloride hydrochloride thus obtained melts at about 222-225 C. to a colorless frothy liquid.

The acetone-methanol filtrate, obtainedabove, is concentratedto a-viscous orange syrup by evaporation in The resultant solid the hoodat room temperature. The syrup is treated with r 100 of-acetone and stirred and scratched until it crystalhzes. It ls recrystallized by dissolving in 50 ml. of. warm methanol, cooling, andslowly adding 500 ml.

ofhcetone with stirring and seeding. The crystalline product is filtered and in the steam cabinet. It is 1 (2 diethylaminoethyl) 2 chloromethyl 5 methoxy-4-pyridone dihydrochloride.

Example '14.

To a stirred suspension of 0.7 g. of I-(Z-diethylaminoethyl)-2-chloroethyl-S-methoxy-l-pyridone dihydrochloride in 10 mlj of absolute ethanol is added 0.7 g. of l-aminopentane. The reaction mixture is refluxed one hour. The clear solution thus obtained'is diluted with it) ml. of anhydrous ethyl ether. A white precipitate is formed. it is suction filtered, washed with cold absolute ethanol, and dried in the steam cabinet. The watersoluble crystals of 2,2-diethyl-7-methoxy-8-oxo-l,2,3,4- tetrahydro-8H-pyrid0[1.2]pyrazinium chloride melt at about 255-257 C. with decomposition to a frothy red liquid;

A particularly convenient synthesis of the above quaternary salt can also be elected by directly treating the unseparated products of the preceding example with L aminopentane, for either product, treated with l aminopentane, yields this salt. If desired, the hydrochloride of 2,2-diethyl-7-methoxy-8-oxo l,2,3,4 tetrahydro-8H- pyrido[1.2]pyrazinium chloride may be reconstituted by treatment with hydrogen chloride in alcohol-acetone solution.-

p Example 15 V .To a stirred mixture of 60 ml. of absolute ethanol and 7 22.0 g. of .2,2-diethyl-7-methoxy-8-oxo-l,2,-3,4-tetrahydro-8H-pyrido[l.2]pyrazinium chloride hydrochloride, 12.4 g. of l-aminopentane is addedi The reaction mixture is stirred and refluxed on the steam bath for 30 minutes. The resultant white solid is filtered hot, washed on the filter with 20 ml. of cold absolute ethanol and dried in the steam cabinet. The 2,2-diethyl-7-methoxy-8- oxo '1,2,3,4-tetrahydro-8H-pyrido[1.2]pyrazinium .chloride is obtained as water-soluble crystals decomposing at 257-261 C. to a fro thy red liquid.

What is claimed is:

1. A compound of the structural formula wherein R is a member of the class consisting of lower alkyl and lower hydroxyalkyl radicals and n is a positive integer smaller than 3.

2. A compound of the structural formula wherein R is a lower alkyl radical. 1

3. 2 ethyl 7 methoxy 1,2,3,4 tetrahydro 8H- pyrido 1.2]pyrazin-8-one.

4. 2 propyl 7 methoxy 1,2,3,4 tetrahydro 8H- pyrido[ 1.2]pyrazin-8-0ne. v

5. A compound of the structural formula wherein R is a lower hydroxyalkyl radical.

6. 2 (2 hydroxyethyl) 7 1 methoxy 1,2,3,4 tetrahydro-8H-pyrido[ l .2] pyrazin-S-one.

7. 2 (3 hydroxypropyl) 7 methoxy 1,2,3,4 tetrahydro-SH-pyrido[1.2]pyrazin-8-one.

s. 2 3 hydroxybutyl) 7 methoxy l,2,3,4 tetrahydro-SH-pyrido 1.2]pyrazin-8-one.

9 '10 9. A compound of the structural formula 11. 1 (3 chloropropyl) 2 chloromethyl 5 meth- O oxy-4-pyridone.

References Cited in the file of this patent I 6 UNITED STATES PATENTS CHr-CI 2,740,786 Schwab Apr. 3, 1956 OTHER REFERENCES Campbell et 8.1.: 101.11. Organic Chemistry, vol. 15, pp.

wherein n is a positive integer smaller than 3. 221-226 1950 10. 1 (2 chloroethyl) 2 chloromethyl 5 meth- Heyns et a1.: Chemische Berichte, vol. 87, pages 1377- oxy-4 pyridone. 1384 (1954).

kHz-(CH1) 11-01 UNITED STATES PATENT. OFFICE CERTIFICATE OF CORRECTION Patent No, 2,999,860 September l2 1961 Carl Peter Krimmel It is hereby certified that error appears in the above numbered patent requiring correction and that the said Letters Patent should read as corrected below.

Column 6, line 25, for "hydroxbutyD'" read hydroxybutyl) column 7, line l3 for "-7-methyl-1 read -7meth0xyl,

Signed and'sealed this 24th day of April 1962.

(SEAL) Attest:

ESTON G. JOHNSON DAVID LADD Attesting Oi'ficer Commissioner of Patents 

1. A COMPOUND OF THE STRUCTURAL FORMULA 